Multienzyme One-Pot Cascade for the Stereoselective Hydroxyethyl Functionalization of Substituted Phenols.

Stefan E Payer,Silvia M Glueck,Florian Hamm,Hannah Pollak,Kurt Faber,Filip Juričić,Benjamin Schmidbauer

doi:10.1021/acs.orglett.8b02058

Abstract

The operability and substrate scope of a redesigned vinylphenol hydratase as a single biocatalyst or as part of multienzyme cascades using either substituted coumaric acids or phenols as stable, cheap, and readily available substrates are reported.

Highlights

The ability of enzymes to work under ambient conditions in a highly selective manner evidences biocatalysis as a powerful concept for eco-friendly synthetic applications of valuable compounds, which enormously benefit from the rapid progress in molecular biology and biotechnology
The use of two or even more enzymes in a cascadewise fashion can considerably improve the efficiency of a multistage synthesis by circumventing the isolation of intermediates, saving time, resources, and reagents while simultaneously diminishing the consumption of energy and the production of waste.[2−4] Further aspects such as the overall cascade should run energetically downhill, and the introduction of an appropriate cofactor recycling in the case of cofactor-dependent enzymes and a preferably irreversible last step in order to increase the overall yield need to be taken into account
We present a redox-neutral, atom-efficient multienzyme system for the production of valuable (S)-1-(4hydroxyphenyl)ethanols as an alternative to biocatalytic redox processes (Scheme 1).[5−9] A promiscuous para-vinylphenol hydratase activity of ferulic acid decarboxylase from Enterobacter sp.,[10−12] which was significantly improved by a rational redesign approach (FDC* mutant),[13] was merged with a prefixed decarboxylation step catalyzed by the wild-type enzyme (FDC).[14]

Summary

Organic Letters

We evaluated the substrate scope of two vinylphenol hydratases that were rationally designed from a ferulic acid decarboxylase and found them to perform the (S)selective addition of water with high conversion and stereoselectivities restricted to vinylphenols bearing various substituents on the aromatic core. These hydratases lack the dependency on bicarbonate required as the hydration cofactor by the wild-type decarboxylase, facilitating the implementation of this biotransformation into multienzyme cascades. Experimental details and supplementary results, preparation of substrates and reference material, and compound characterization (PDF)

■ ACKNOWLEDGMENTS

Findings

■ REFERENCES